Leishmanial infections are worldwide in distribution, occurring in Africa, North and South America, Southern Europe, and Asia. The clinical manifestations of leishmaniasis are extremely varied and include visceral (VL), cutaneous (CL), diffuse cutaneous, and mucosal (ML) disease. There are an estimated 15-20 million cases of leishmaniasis worldwide and there are neither leishmania vaccines nor standardized tests for diagnosis. The existing treatment is expensive and often requires hospitalization. Notwithstanding, the leishmaniases are excellent candidates for the development of vaccines, antigen-based therapeutics, cytokine therapy, and effective diagnostics. The goal of this project is to develop leishmania recombinant antigens for vaccine development for use in VL. We have developed a vaccine for CL and ML that is now in clinical trials. This vaccine does not appear to be optimized for VL in animal models. There could be two reasons for this; 1) either the antigens or 2) the adjuvant/delivery system are not optimized to induce adequate protection against VL. In this proposal we will address both of these possibilities by identifying T cell antigens of the L. donovani complex, and using new adjuvants, DNA immunization, or combinations (i.e. prime boost protocols) to develop an effective vaccine for humans and dogs.